Katz J L, Terry P, Witkin J M
Psychobiology Laboratory, NIDA Addiction Research Center, Baltimore, Maryland 21224.
Life Sci. 1992;50(18):1351-61. doi: 10.1016/0024-3205(92)90286-x.
The present study compared the behavioral and toxic effects of cocaine and its ethanol derived metabolite, cocaine ethyl-ester (cocaethylene). Both drugs produced qualitatively similar psychomotor stimulant effects. Cocaine and cocaethylene increased locomotor activity in mice, with cocaine approximately four times more potent than cocaethylene. The durations of action of ED75 doses of each of the drugs were comparable. Each of the drugs also produced stimulation of operant responding in rats. In rats and squirrel monkeys trained to discriminate cocaine injections from saline, cocaine was approximately three to five times more potent than cocaethylene in producing these cocaine-like interoceptive effects. In contrast to the behavioral effects, cocaine and cocaethylene were equipotent in producing convulsions, and cocaethylene was more potent than cocaine in producing lethality. These results suggest that the conversion of cocaine to cocaethylene with simultaneous cocaine and alcohol use may produce an increased risk of toxicity due to a decrease in the potency of cocaethylene in producing psychomotor stimulant effects, and its increased potency in producing toxicity.
本研究比较了可卡因及其乙醇衍生代谢物可卡因乙酯（可口乙古）的行为效应和毒性作用。两种药物产生的定性心理运动刺激效应相似。可卡因和可口乙古增加了小鼠的运动活性，可卡因的效力约为可口乙古的四倍。每种药物的ED75剂量的作用持续时间相当。每种药物还能刺激大鼠的操作性反应。在经过训练能区分可卡因注射和生理盐水注射的大鼠和松鼠猴中，在产生这些类似可卡因的内感受效应方面，可卡因的效力约为可口乙古的三到五倍。与行为效应相反，可卡因和可口乙古在引发惊厥方面效力相当，而可口乙古在产生致死性方面比可卡因更具效力。这些结果表明，同时使用可卡因和酒精时可卡因向可口乙古的转化可能会增加毒性风险，这是由于可口乙古产生心理运动刺激效应的效力降低，而其产生毒性的效力增加。
